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Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection

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Abstract

Aspergillus terreus causes invasive aspergillosis (IA) in immunocompromised patients. Treatment is complicated by intrinsic resistance to amphotericin B and thereby contributing to a high mortality. Therefore, we conducted in vitro studies to investigate the effectivity of adjunctive recombinant interferon-γ immunotherapy. We describe a pediatric patient with A. terreus IA who received adjunctive recombinant interferon-γ (rIFNγ) immunotherapy. In vitro studies were conducted to investigate the capacity of rIFNγ to improve antifungal host defense in terms of fungal killing ability and the release of pro-inflammatory cytokines in cells of the patient as well as healthy controls. An 8-year-old female pediatric patient with leukemia developed A. terreus IA. She clinically deteriorated and had high serum galactomannan levels despite broad antifungal therapy. Therefore, adjunctive immune stimulatory therapy with rIFNγ was initiated. After 3 weeks of treatment, galactomannan levels decreased and the patient clinically showed improvement. Addition of rIFNγ boosted the capacity of monocytes of healthy volunteers to mount TNFα and IL-1β cytokine responses to Escherichia coli LPS, and increased TNFα response to both A. terreus and Aspergillus fumigatus. Monocytes isolated from the patient’s blood demonstrated a similar augmented cytokine induction in response to rIFNγ. In addition, rIFNγ increased the capacity of monocytes from healthy volunteers as well as monocytes from the patient to kill A. terreus spores. Adjuvant immunotherapy with rIFNγ might be a promising additional treatment strategy that could be used to improve outcome in patients with refractory invasive A. terreus infections or other resistant invasive Aspergillus infections.

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Acknowledgments

We thank H.A.L. van der Lee for providing us with photographs of specimens.

Funding

This work was not supported by financial funding or other sources of pharmaceutical or industry support.

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Authors and Affiliations

  1. Department of Pediatrics, Radboudumc Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, the Netherlands

    Eemke L. Assendorp & Natasja Dors

  2. Experimental Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands

    Mark S. Gresnigt & Evelien G. G. Sprenkeler

  3. Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands

    Jacques F. Meis

  4. Center of Expertise in Mycology, Radboud University Medical Center/Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands

    Jacques F. Meis

  5. Department of Pediatrics, Bernhoven Hospital, Uden, the Netherlands

    Jan W. M. van der Linden

  6. Department of Pediatric Infectious Diseases and Immunology, Radboudumc Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, the Netherlands

    Stefanie S. V. Henriet

Authors
  1. Eemke L. Assendorp
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  2. Mark S. Gresnigt
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  3. Evelien G. G. Sprenkeler
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  4. Jacques F. Meis
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  5. Natasja Dors
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  6. Jan W. M. van der Linden
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  7. Stefanie S. V. Henriet
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Corresponding author

Correspondence to Jan W. M. van der Linden.

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Conflict of interest

J.F.M. received grants from Astellas, Merck, and Basilea. He has been a consultant to Basilea Scynexis and Merck and received speaker fees from Merck, Pfizer, Gilead, TEVA, and United Medical. All other authors declare they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Assendorp, E.L., Gresnigt, M.S., Sprenkeler, E.G.G. et al. Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection. Eur J Clin Microbiol Infect Dis 37, 1915–1922 (2018). https://doi.org/10.1007/s10096-018-3325-4

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  • DOI: https://doi.org/10.1007/s10096-018-3325-4

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